With the recent addition of a cyclotron and radiochemistry facility to our Nuclear Medicine Division, St Jude Children's Research Hospital investigators now have access to a wide variety of both known and novel radiotracers for positron emission tomography (PET) imaging. The small animal PET scanner that is the subject of this application is requested to expand the capabilities of our existing Animal Imaging Center (AIC) to take full advantage of this newly acquired access to PET radiotracers. We are currently engaged in several collaborative projects using PET radiotracers for preclinical studies. These studies, while very powerful and quantitative, are limited in that without a small animal PET scanner, they require sacrifice and dissection of the subject animals and yield data at only discrete time points. The real strength of PET lies in the ability to make such quantitative measurements of in vivo biochemical processes in real time. Furthermore, the ability to make repeated measurements in the same animal over hours, days or weeks allows assessment of longitudinal parameters such as therapy response, subject-specific titration of drug doses and regulation of biochemical processes in response to stimuli. Similarly, new therapeutic discovery would benefit from the in vivo pharmacokinetic studies possible in real time with small animal PET using custom designed radiotracers. All of these latter studies are much more complex and expensive, or simply impossible, using dissection methods rather than in vivo imaging. In addition, our institution has a diverse collection of unique preclinical models (both transgenic and xenograft) with which to study disease processes and test new therapeutic regimens in pediatric oncology. All of these models could greatly benefit from the unique capabilities of PET imaging to enhance current research efforts. Dissection studies that assess tumor pathophysiology (as we do now) are challenging in orthotopic xenograft models where exact tumor location is less predictable. Furthermore, non-terminal imaging is the only practical method for studies of transgenic models due to the cost and difficulty of animal breeding. The AIC serves as a core resource to all St Jude investigators and is funded in part by our NCI Comprehensive Cancer Center grant. We have identified 12 faculty investigators who would be the primary users of this core technology, most of whom have funded research efforts on one or multiple NIH grants and are engaged in multi-disciplinary collaborative projects with one or more investigators at St Jude and at other institutions. They represent 6 academic departments and 4 Cancer Center Programs with a variety of expertise in imaging, molecular and cellular oncology, pharmacokinetics, therapeutic design and medicinal chemistry. The addition of a small animal PET scanner will allow us to fully capture this environment of collaboration and the institution's investment in Nuclear Medicine research and will facilitate St Jude's commitment to outstanding translational research. PUBLIC HEALTH RELEVANCE: St Jude Children's Research Hospital is dedicated to the study and treatment of catastrophic disease in children. With the recent addition of a cyclotron and radiochemistry facility to our Nuclear Medicine Division, St Jude Children's Research Hospital investigators now have access to a variety of novel radioactive drugs for a medical imaging procedure called positron emission tomography. The addition of a preclinical PET imaging camera will allow us to take full advantage of both this recent investment in Nuclear Medicine research and the existing variety of preclinical models unique to our institution, thus facilitating St Jude's commitment to outstanding translational research.